Today's laboratory attempts to meet the dramatically increasing need for analytical data brought about by the increased pace of new product development, increased research, demands for stricter quality control, and the like. Labs deliver data in a timely, cost-efficient way while ensuring precise results, clear documentation, and minimal use of skilled (and, therefore, expensive) personnel. For example, automated systems have been proposed to assess a variety of biological phenomena, including, e.g., expression levels of genes in response to selected stimuli (Service (1998) “Microchips Arrays Put DNA on the Spot” Science 282:396-399), high throughput DNA genotyping (Zhang et al. (1999) “Automated and Integrated System for High-Throughput DNA Genotyping Directly from Blood” Anal. Chem. 71:1138-1145) and many others. Similarly, integrated systems for performing mixing experiments, DNA amplification, DNA sequencing and the like are also available (See, e.g., Service (1998) “Coming Soon: the Pocket DNA Sequencer” Science 282: 399-401).
Improvements in laboratory automation continually increase the productivity of laboratory workers and provide for more precise results, clearer documentation and the like, as compared to the performance of unautomated tasks. The automation of laboratory procedures using devices and/or systems dedicated to particular tasks in the laboratory substantially enhances the speed and reproducibility of a variety of experimental tasks. Product research, regulatory approval and quality control in industries such as pharmaceuticals, chemicals, and biotechnology routinely involve the testing of thousands (or even hundreds of thousands) of samples.
Automated systems typically perform, e.g., repetitive fluid handling operations (e.g., pipetting) for transferring material to or from reagent storage systems such as microtiter trays, which are used as basic container elements for a variety of automated laboratory methods. Similarly, the systems manipulate, e.g., microtiter trays and control a variety of environmental conditions such as temperature, exposure to light or air, and the like.
Many such automated systems are commercially available. For example, a variety of automated systems are available from the Zymark Corporation (Zymark Center, Hopkinton, Mass.), which utilize various Zymate systems, which typically include, e.g., robotics and fluid handling modules. Similarly, the common ORCA® robot, which is used in a variety of laboratory systems, e.g., for microtiter tray manipulation, is also commercially available, e.g., from Beckman Coulter, Inc. (Fullerton, Calif.).
More recently, microfluidic systems have established the potential for even greater automation and laboratory productivity increases. In these microfluidic systems, automated fluid handling and other sample manipulations are controlled at the microscale level. Such systems are now commercially available. For example, the Hewlett-Packard (Agilent Technologies) HP2100 bioanalyzer utilizes LabChip™ technology to manipulate extremely small sample Volumes. In this “lab-on-a-chip,” system, sample preparation, fluid handling and biochemical analysis steps are carried out within the confines of a microchip. The chips have microchannels fabricated, e.g., in glass, providing interconnected networks of fluid reservoirs and pathways.
While many automated systems are now available, the application of automated systems to non-routine sample handling and analysis remains challenging. In particular, the application of automation to new technologies in the field of molecular biology would be desirable. For example, some of the most significant new classes of techniques in molecular biology are found in the field of rapid forced molecular evolution. In rapid evolution processes, diversity is generated in nucleic acids of interest via mutation, recombination, or other mechanisms, which are screened for one or more desirable activities, or encoded activities. These processes are repeated until a nucleic acid possessing or encoding a desired activity level is produced. The present invention provides significant new automated systems and methods which facilitate nucleic acid shuffling and other diversity generating/screening processes of interest.